Editorial Material
Hematology
Weijie Li
Summary: In this study, Calabria et al demonstrate that intrathymic delivery of AAV vectors leads to site-specific integration within TCR genes close to DNA breaks created by RAG enzymes during V(D)J recombination.
Editorial Material
Rheumatology
Sarah Onuora
Summary: Targeting inhibitor of apoptosis proteins (IAPs) can ameliorate ANCA-associated vasculitis by enhancing fatty acid oxidation in neutrophils.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Chemistry, Analytical
Christoph Gstottner, Andrei Hutanu, Sacha Boon, Aurelia Raducanu, Klaus Richter, Markus Haindl, Raphael Ruppert, Elena Dominguez-Vega
Summary: Ion pairing-reverse phase-liquid chromatography (IP-RP-LC) has been demonstrated for the first time to characterize the integrity of rAAV genomes. This technique is user-friendly, requires minimal sample preparation, has high reproducibility, and allows for further peak characterization. It adds significant analytical value to the assessment of rAAV genomes.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Lauren F. Barnes, Benjamin E. Draper, Justin Kurian, Yu-Ting Chen, Tatiana Shapkina, Thomas W. Powers, Martin F. Jarrold
Summary: In this study, charge detection mass spectrometry (CDMS) was used to measure the molecular weight distribution of the extracted genome of interest (GOI) from recombinant AAV vectors. The results showed that CDMS is a rapid and powerful tool for evaluating genome integrity in gene therapy products.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Terence R. Flotte, Oguz Cataltepe, Ajit Puri, Ana Rita Batista, Richard Moser, Diane McKenna-Yasek, Catherine Douthwright, Gwladys Gernoux, Meghan Blackwood, Christian Mueller, Phillip W. L. Tai, Xuntian Jiang, Scot Bateman, Spiro G. Spanakis, Julia Parzych, Allison M. Keeler, Aly Abayazeed, Saurabh Rohatgi, Laura Gibson, Robert Finberg, Bruce A. Barton, Zeynep Vardar, Mohammed Salman Shazeeb, Matthew Gounis, Cynthia J. Tifft, Florian S. Eichler, Robert H. Brown, Douglas R. Martin, Heather L. Gray-Edwards, Miguel Sena-Esteves
Summary: This study presents the results of AAV gene therapy in two patients with infantile TSD. The treatment was well tolerated without vector-related adverse events, and demonstrated an increase and stability of HexA activity in the cerebrospinal fluid. One patient showed disease stabilization, while the other experienced disease progression after treatment.
Article
Biochemistry & Molecular Biology
Qin Huang, Albert T. J. Chen, Ken Y. Chan, Hikari Sorensen, Andrew Barry, Bahar Azari, Qingxia G. Zheng, Thomas Beddow, Binhui Zhao, Isabelle J. Tobey, Cynthia Moncada-Reid, Fatma-Elzahraa R. Eid, Christopher D. Walkey, M. Cecilia A. Ljungberg, William E. Lagor, Jason Heaney, Yujia Chan, Benjamin Deverman
Summary: Viruses have evolved the ability to enter cells by interacting with cell macromolecules, and in this study, researchers engineered AAV capsids that transduce the brain by interacting with specific proteins expressed on the blood-brain barrier. These modified capsids showed enhanced central nervous system tropisms and enabled saturation mutagenesis and machine learning exploration of the capsid sequence space. It was also found that most AAV capsids selected for their ability to cross the blood-brain barrier in mice used proteins not present in primates. This work demonstrates the potential of AAV capsids for targeted gene delivery.
Article
Biotechnology & Applied Microbiology
Dhwanil A. Dalwadi, Andrea Calabria, Amita Tiyaboonchai, Jeffrey Posey, Willscott E. Naugler, Eugenio Montini, Markus Grompe
Summary: Research found a high frequency of chromosomal integrations of recombinant adeno-associated viral vectors in liver cells, with most inserted sequences heavily rearranged and accompanied by deletions of host genomic sequences at integration sites. This indicates a certain risk associated with rAAV integration.
Article
Multidisciplinary Sciences
Megha Subramanian, James McIninch, Ivan Zlatev, Mark K. Schlegel, Charalambos Kaittanis, Tuyen Nguyen, Saket Agarwal, Timothy Racie, Martha Arbaiza Alvarado, Kelly Wassarman, Thomas S. Collins, Tyler Chickering, Christopher R. Brown, Karyn Schmidt, Adam B. Castoreno, Svetlana Shulga-Morskaya, Elena Stamenova, Kira Buckowing, Daniel Berman, Joseph D. Barry, Anna Bisbe, Martin A. Maier, Kevin Fitzgerald, Vasant Jadhav
Summary: The authors propose an RNA interference-based switch to control AAV transgene expression. They use RNAi to silence transgene expression and then recover it using REVERSIR oligonucleotides. This approach has the potential for clinical application in gene therapy.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Megan S. Keiser, Paul T. Ranum, Carolyn M. Yrigollen, Ellie M. Carrell, Geary R. Smith, Amy L. Muehlmatt, Yong Hong Chen, Joel M. Stein, Ronald L. Wolf, Enrico Radaelli, Timothy J. Lucas, Pedro Gonzalez-Alegre, Beverly L. Davidson
Summary: The preclinical safety study of RNA interference (RNAi) for spinocerebellar ataxia type 1 therapy showed toxicity in nonhuman primates but not in rodents, due to unexpected AAV inverted terminal repeat transcriptional activity that was mitigated by altering the RNAi expression environment.
Article
Multidisciplinary Sciences
Agata Antepowicz, Omar Habib, Freja Kirsebom, Cecilia Johansson, Deborah R. Gill, Stephen C. Hyde
Summary: In this study, gene delivery approaches using recombinant adeno-associated virus and simian immunodeficiency virus vectors were utilized to achieve sustained in vivo production of Palivizumab in a murine model. Pre-treatment with Palivizumab-expressing vectors provided complete protection against RSV-induced weight loss. This approach offers prophylaxis against RSV infection, potentially reducing treatment costs in vulnerable populations.
SCIENTIFIC REPORTS
(2021)
Article
Biochemical Research Methods
James Zengel, Yu Xin Wang, Jai Woong Seo, Ke Ning, James. N. N. Hamilton, Bo Wu, Marina Raie, Colin Holbrook, Shiqi Su, Derek. R. R. Clements, Sirika Pillay, Andreas. S. S. Puschnik, Monte. M. M. Winslow, Juliana Idoyaga, Claude. M. M. Nagamine, Yang Sun, Vinit. B. B. Mahajan, Katherine. W. W. Ferrara, Helen. M. M. Blau, Jan. E. E. Carette
Summary: SELECTIV is an efficient method that enables tissue-specific transgene expression in mice through AAV receptor overexpression. It significantly improves the efficiency and specificity of AAV transduction in various cell types by coupling AAV vectors with Cre-inducible overexpression of the multi-serotype AAV receptor, AAVR. The enhanced efficacy and exquisite specificity of SELECTIV have broad applications in the development of new mouse model systems and gene delivery in vivo using AAV.
Article
Multidisciplinary Sciences
Trevor J. Gonzalez, Katherine E. Simon, Leo O. Blondel, Marco M. Fanous, Angela L. Roger, Maribel Santiago Maysonet, Garth W. Devlin, Timothy J. Smith, Daniel K. Oh, L. Patrick Havlik, Ruth M. Castellanos Rivera, Jorge A. Piedrahita, Mai K. ElMallah, Charles A. Gersbach, Aravind Asokan
Summary: Researchers have successfully generated a cross-species compatible AAV (ccAAVs) vector using a viral evolutionary approach, and discovered a highly potent new variant AAV.cc47. AAV.cc47 demonstrated enhanced transduction efficiency compared to AAV serotype 9 in mouse, pig, and non-human primate models, showing great potential for gene therapy. This study focuses on investigating cross-species delivery of AAV and provides new theoretical insights for translating gene therapy into clinical applications.
NATURE COMMUNICATIONS
(2022)
Review
Cardiac & Cardiovascular Systems
Huili Zhang, Qi Zhan, Biao Huang, Yigang Wang, Xiaoyan Wang
Summary: Gene therapy has brought significant advancements to the field of medicine, offering hope for patients with various diseases. Adeno-associated virus (AAV) has shown great potential as a treatment tool due to its safety, sustainable gene expression, and low immunogenicity, especially in the field of cardiovascular disease.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Medicine, Research & Experimental
Darnel Prakoso, Mitchel Tate, Miles J. De Blasio, Rebecca H. Ritchie
Summary: Diabetes increases the prevalence of heart failure by 6-8-fold, independent of other comorbidities, such as hypertension and coronary artery disease, leading to a condition known as diabetic cardiomyopathy. Current pharmacological treatments can delay disease progression, but gene therapy using adeno-associated viral vectors (AAV) is being explored as a potential lifelong cure for diabetic cardiomyopathy.
Review
Microbiology
Lena C. Schroeder, Derk Frank, Oliver J. Mueller
Summary: Cardiac-targeted transgene delivery provides new treatment opportunities for cardiovascular diseases by using cis-regulatory elements to restrict gene transfer and protect extracardiac organs. Tissue-specific promoters for targeted transcription in specific cardiac cells have been identified, some of which are induced at pathological states and could potentially act as induction-by-disease switches in gene therapy.
Article
Multidisciplinary Sciences
Markus B. Heckmann, Ashraf Yusuf Rangrez, Daniel Finke, Andreas Jungmann, Julia S. Kreuer, Alexandra Rosskopf, Nesrin Schmiedel, Hugo A. Katus, Norbert Frey, Oliver J. Mueller
SCIENTIFIC REPORTS
(2020)
Article
Cardiac & Cardiovascular Systems
Harald Herrmann, Eva Cabet, Nicolas R. Chevalier, Julia Moosmann, Dorothea Schultheis, Jan Haas, Mirjam Schowalter, Carolin Berwanger, Veronika Weyerer, Abbas Agaimy, Benjamin Meder, Oliver J. Muller, Hugo A. Katus, Ursula Schlotzer-Schrehardt, Patrick Vicart, Ana Ferreiro, Sven Dittrich, Christoph S. Clemen, Alain Lilienbaum, Rolf Schroeder
Article
Nutrition & Dietetics
Patricia M. Rusu, Andrea Y. Chan, Mathias Heikenwalder, Oliver J. Mueller, Adam J. Rose
Summary: Dietary amino acid (AA) restriction, particularly essential amino acid (EAA) restriction, promotes hyperdipsia. Restriction of threonine (Thr) or tryptophan (Trp) is essential for hyperdipsic effect, and liver/hepatocyte-derived FGF21 is required for this phenomenon. Introducing Thr de novo biosynthesis in hepatocytes can reverse hyperdipsia during dietary amino acid restriction.
Article
Cardiac & Cardiovascular Systems
Daniel Ritter, Madeleine Goeritzer, Arne Thiele, Annelie Blumrich, Niklas Beyhoff, Katja Luettges, Elia Smeir, Juliane Kasch, Jana Grune, Oliver J. Mueller, Robert Klopfleisch, Carsten Jaeger, Anna Foryst-Ludwig, Ulrich Kintscher
Summary: The study demonstrates that the LXR agonist can prevent subendocardial damage, improve global longitudinal strain and E/e' ratio, accompanied by an upregulation of cardiac polyunsaturated fatty acids levels.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Oncology
Daniel Finke, Markus B. Heckmann, Janek Salatzki, Johannes Riffel, Esther Herpel, Lucie M. Heinzerling, Benjamin Meder, Mirko Voelkers, Oliver J. Mueller, Norbert Frey, Hugo A. Katus, Florian Leuschner, Ziya Kaya, Lorenz H. Lehmann
Summary: Immune checkpoint inhibitors are transforming cancer treatment but can lead to immune-related adverse events, including ICI-associated myocarditis. The transcriptional alterations associated with this rare but severe phenomenon remain poorly characterized. By comparing transcriptomics, potential pathomechanisms like the GBP5 protein were identified that may help in diagnosing and identifying patients at risk for ICIM.
Article
Biochemistry & Molecular Biology
Georg Lutter, Thomas Puehler, Lukas Cyganek, Jette Seiler, Anita Rogler, Tanja Herberth, Philipp Knueppel, Stanislav N. Gorb, Janarthanan Sathananthan, Stephanie Sellers, Oliver J. Mueller, Derk Frank, Irma Haben
Summary: In this study, biodegradable PCL nanofiber scaffolds were used as a matrix for the generation of tissue-engineered heart valves with human ECFCs and iMSCs. Results showed good cell adhesion and distribution on PCL fibers, with coated fibers increasing cell numbers only at early stages. Mechanical properties of seeded PCL scaffolds were comparable to native heart valves, indicating successful tissue engineering of heart valves with human cells on a biodegradable scaffold.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sebastian Wundersitz, Cristina Pablo Tortola, Sibylle Schmidt, Ramon Oliveira Vidal, Melanie Kny, Alexander Hahn, Lukas Zanders, Hugo A. Katus, Sascha Sauer, Christian Butter, Friedrich C. Luft, Oliver J. Mueller, Jens Fielitz
Summary: Overexpression of TFEB for the treatment of ALP-related diseases may have adverse effects on cardiac stress response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Martina E. Spehlmann, Ashraf Y. Rangrez, Dhiraj P. Dhotre, Nesrin Schmiedel, Nikita Chavan, Corinna Bang, Oliver J. Mueller, Yogesh S. Shouche, Andre Franke, Derk Frank, Norbert Frey
Summary: Growing evidence suggests that patients with heart failure (HF) have an altered gut microbiome. This study used a mouse model to investigate the association between the severity and progression of HF and the composition of gut microbiome and circulating metabolites. The results showed that gut bacterial diversity was significantly lower in mice with HF compared to controls, and the abundance and grouping of several bacteria differed based on the severity of cardiac dysfunction. Metabolic alterations, such as reduced short-chain fatty acids and an increase in primary bile acids, were strongly correlated with the differential abundance of distinct bacteria in HF.
Review
Medicine, General & Internal
Klaus Kallenbach, Anca Remes, Oliver J. Mueller, Rawa Arif, Marcin Zaradzki, Andreas H. Wagner
Summary: The researchers first provided an overview of the historical background and characterization of Marfan syndrome, and found that gene therapy, which is used in genetic diseases, may have a therapeutic effect on this disorder.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Medicine, General & Internal
Xiling Zhang, Thomas Puehler, Lars Sondergaard, Derk Frank, Hatim Seoudy, Baland Mohammad, Oliver J. Mueller, Stephanie Sellers, David Meier, Janarthanan Sathananthan, Georg Lutter
Summary: This article introduces the newest devices for transcatheter mitral valve repair and replacement and presents clinical trial data to identify current challenges and directions for future research.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cell Biology
Ricarda Haustein, Felix A. Trogisch, Merve Keles, Susanne Hille, Manuela Fuhrmann, Nina Weinzierl, Shruthi Hemanna, James Thackeray, Yanliang Dou, Carolin Zwadlo, Natali Froese, Julio Cordero, Frank Bengel, Oliver J. Mueller, Johann Bauersachs, Gergana Dobreva, Joerg Heineke
Summary: Endothelial-derived CTRP9 plays a protective role in diabetic cardiomyopathy by improving insulin signaling, glucose uptake, and oxidative energy production in the heart. CTRP9 also acts as an anti-inflammatory mediator, reducing leukocyte accumulation in the myocardium.
Article
Medicine, General & Internal
Nina Sophie Pommert, Xiling Zhang, Thomas Puehler, Hatim Seoudy, Katharina Huenges, Jan Schoettler, Assad Haneya, Christine Friedrich, Janarthanan Sathananthan, Stephanie L. Sellers, David Meier, Oliver J. Mueller, Mohammed Saad, Derk Frank, Georg Lutter
Summary: Transaortic transcatheter aortic valve implantation via intercostal access provides a safe and effective treatment option for aortic valve stenosis, with comparable outcomes to the traditional transaortic approach but fewer complications and shorter hospital stays.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Microbiology
Lena C. Schroeder, Derk Frank, Oliver J. Mueller
Summary: Cardiac-targeted transgene delivery provides new treatment opportunities for cardiovascular diseases by using cis-regulatory elements to restrict gene transfer and protect extracardiac organs. Tissue-specific promoters for targeted transcription in specific cardiac cells have been identified, some of which are induced at pathological states and could potentially act as induction-by-disease switches in gene therapy.
Review
Cardiac & Cardiovascular Systems
Xiling Zhang, Thomas Puehler, Derk Frank, Janarthanan Sathananthan, Stephanie Sellers, David Meier, Marcus Both, Philipp Blanke, Hatim Seoudy, Mohammed Saad, Oliver J. Mueller, Lars Sondergaard, Georg Lutter
Summary: This review discusses the expansion indications of TAVR, including concerns about long-term durability and the advantages of surgery in certain situations.
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Xiling Zhang, Thomas Puehler, Jette Seiler, Stanislav N. Gorb, Janarthanan Sathananthan, Stephanie Sellers, Assad Haneya, Jan-Hinnerk Hansen, Anselm Uebing, Oliver J. Mueller, Derk Frank, Georg Lutter
Summary: Although transcatheter pulmonary valve replacement has shown favorable results as an alternative treatment for pulmonary valve disease, many patients are still not suitable candidates for this procedure. One of the significant future challenges is to expand the use of transcatheter pulmonary valve replacement to a broader patient population.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
